Which would you prefer, a gain of $20 in 12 months or of $22 in 13 months? Most people would wait the extra month to gain the extra $2. Ask yourself the same question 365 days later: which would you prefer, $20 today or $22 in a month? Now most people would select the immediate gain of $20; a reversal in preferences. Sitting in a clinic, most drug users state a preference for avoiding drug use later in the day. Hours later, confronting an immediately available drug, their preferences reverse. These observations reveal that humans make choices by comparing the subjective values of rewards and that these values depend not just on how large a reward is but when that reward will be received. The longer gratification is delayed; the less desirable a reward appears. Empirical data suggests that this decrease in desirability occurs most abruptly at short delays and more gradually as delays increase. Perhaps just as interesting is the observation that essentially all vertebrates appear to show a similar pattern. What then, is the neural mechanism that sets a subjective value on delayed rewards? Neurobiological studies of decision-making have largely avoided this issue. In this application we propose to extend existing neurobiological studies of decision-making into the domain of choice-in-time. We propose to undertake this study with a combination of behavioral, physiological and functional magnetic resonance imaging techniques and to test two hypotheses that seek to explain choice-in-time: a standard physiological model and the dominant two-system model of economic theory. Specifically, we propose to test the hypothesis that either of these models can account for the activity of the posterior parietal cortex and the ventral striatum under a range of conditions. Pathological influences of delays on decision making are pervasive in disease. Delays distort the decisions made by children with attention-deficit disorder, pathological gamblers, drug abusers, smokers, alcoholics, cocaine and heroin addicts. Despite the fact that an abnormal sensitivity to delays controls the behavior of all of these patient groups, almost nothing is known about the mechanism of this disorder. We propose a series of experiments aimed at elucidating the basic mechanism that underlies the pathological decision making that marks inappropriate choice-in-time. [unreadable] [unreadable] [unreadable]